Toluene → 4-(4'-Methyl-biphenyl-4-ylmethyl)-2-phenyl-morpholine

HRID 737077Notes

Reaction equation

HRID 737077 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][O:10][CH:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:8]2)=[CH:4][CH:3]=1.[CH3:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[CH3:21][C:22]1[CH:27]=[CH:26][C:25]([C:2]2[CH:20]=[CH:19][C:5]([CH2:6][N:7]3[CH2:12][CH2:11][O:10][CH:9]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[CH2:8]3)=[CH:4][CH:3]=2)=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 79799Tolylboronic acidHCID 578495044-(4-Bromo-benzyl)-2-phenyl morpholine

Product 1

HCID 578494924-(4'-Methyl-biphenyl-4-ylmethyl)-2-phenyl-morpholineYield 20%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

91 mg of 4-(4-Bromo-benzyl)-2-phenyl-morpholine was combined with 56 mg of 4-Methylphenyl boronic acid, 16 mg of tetrakis(triphenylphosphine)palladium(0), 0.92 mL of 2M sodium carbonate solution, 2.5 mL toluene and 1.23 mL ethanol. The reaction mixture was heated in a sealed tube at 120° C. overnight in an oil bath. The reaction mixture was filtered through Celite and concentrated in vacuo. The residue was diluted with 4 mL DCM and 130 mg of MP-TsOH resin (4.2 mmol/g loading) was added and the mixture agitated at room temperature overnight. The solution is filtered and the resin is then washed with 2M N3 in methanol to liberate product. The resin is washed several times with methylene chloride, concentrated in vacuo and purified by reverse phase HPLC. 18.5 mg of product was obtained as oil. ES MS m/z 344, 20% yield

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with 4 mL DCM and 130 mg of MP-TsOH resin (4.2 mmol/g loading)
  4. additionwas added
  5. filtrationThe solution is filtered
  6. washthe resin is then washed with 2M
  7. washThe resin is washed several times with methylene chloride
  8. concentrationconcentrated in vacuo
  9. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-1495aa064d634c04be80618b38e8383e
Source dataset
uspto-grants-2009_09
Patent number
US07595397B2

Reaction notes

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